Abstract |
We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (Ca- EDTA), as an inhibitor for New Delhi metallo-β-lactamase-1 (NDM-1) in vitro antibiotic susceptibility and in a mouse model of sepsis caused by Escherichia coli. Ca- EDTA drastically reduced the MICs of carbapenems for all NDM-producing bacteria [ imipenem (IPM) ≤1-2 μg/ml; meropenem (MEPM) ≤1-4 µg/ml]. In the neutropenic murine model of sepsis, the bacterial burden was further reduced by combination therapy using imipenem/cilastatin sodium (IPM/CS) and Ca- EDTA to 2.3 × 10(3) CFU/liver, compared with 2.9 × 10(4) CFU/liver for IPM/CS alone. These data demonstrated the possibility of Ca- EDTA for clinical applications. In our understanding, this is the first report examining the effect of Ca- EDTA on a mouse sepsis model caused by NDM-1-producing bacteria.
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Authors | Ayumi Yoshizumi, Yoshikazu Ishii, David M Livermore, Neil Woodford, Soichiro Kimura, Tomoo Saga, Sohei Harada, Keizo Yamaguchi, Kazuhiro Tateda |
Journal | Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
(J Infect Chemother)
Vol. 19
Issue 5
Pg. 992-5
(Oct 2013)
ISSN: 1437-7780 [Electronic] Netherlands |
PMID | 23233082
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Imipenem
- Edetic Acid
- beta-Lactamases
- beta-lactamase NDM-1
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Topics |
- Animals
- Anti-Bacterial Agents
(pharmacology, therapeutic use)
- Bacterial Load
(drug effects)
- Colony Count, Microbial
- Disease Models, Animal
- Edetic Acid
(pharmacology)
- Escherichia coli
(drug effects, enzymology)
- Escherichia coli Infections
(drug therapy, microbiology)
- Imipenem
(pharmacology)
- Mice
- Microbial Sensitivity Tests
- Sepsis
(drug therapy, microbiology)
- beta-Lactam Resistance
- beta-Lactamases
(biosynthesis)
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